Abstract

Chronic diseases of the liver (CLD) are major public health concerns worldwide. Steatosis and steatohepatitis associated with Alcoholic Liver Disease (ALD), Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD)/Non-Alcoholic Fatty Liver Disease (NAFLD) and Hepatitis B and C contribute to CLD. Liver fibrosis, occurs in all forms of advanced CLD, the confirmation of which is typically performed by needle biopsy. Imaging approaches for liver diagnosis exist but do not provide sufficient diagnostic accuracy for defining the various stages of fibrosis or steatosis. Therefore, there is a need for improved imaging capabilities to enhance disease diagnosis. Ultrasound-based Photoacoustic Imaging (US-PAI) has recently emerged as a non-invasive, non-ionizing modality, capable of capturing structural details and oxygen saturation changes during disease progression. However, its potential for detecting surrogate MASLD markers, such as collagen and lipids, which are often poorly resolved by other conventional imaging techniques, has yet be investigated in detail. The novelty of this study lies in the innovative use of spectral photoacoustic imaging for the direct detection and quantification of key biomarkers of liver disease, such as fibrosis, collagen, lipids, oxygenated and deoxygenated hemoglobin, in a mouse model of steatotic fatty liver disease. We established that US-PAI, validated with MRI, effectively identified increases in liver adiposity and fibrosis, enabling the non-invasive detection of changes in liver pathology associated with metabolic dysfunction.